- Separating the contributions of anaerobic oxidation of methane and organoclastic sulfate reduction in the overall sedimentary sulfur cycle of marine sediments has benefited from advances in isotope biogeochemistry. Particularly, the coupling of sulfur and oxygen isotopes measured in the residual sulfate pool (δ18OSO4 vs. δ34SSO4). Yet, some important questions remain. Recent works have observed patterns that are inconsistent with previous interpretations. We separate the contributions of oxygen and sulfur isotopes to separating the anaerobic oxidation of methane and organoclastic sulfate reduction into three phases; first evidence from conventional high methane vs low methane sites suggests a clear relationship between oxygen and sulfur isotopes in porewater and the metabolic process taking place. Second, evidence from pure cultures and organic matter rich sites with low levels of methane suggest the signatures of both processes overlap and cannot be differentiated. Third, we take a critical look at the use of oxygen and sulfur isotopes to differentiate metabolic processes. We identify that it is essential to develop a better understanding of the oxygen kinetic isotope effect, the degree of isotope exchange with sulfoxy intermediates as well as establishing their relationships with the cell-specific metabolic rates if we are to develop this proxy into a reliable tool to study the sulfur cycle in marine sediments and the geological record.